Influence of Plasma Tryptophan on Brain 5HT Synthesis and Serotonergic Activity
significant correlations between plasma free tryptophan and CSF 5HIAA concentrations;
raised cortical 5HT concentrations after infusing tryptophan.
increased uptake when bolus free tryptophan was raised and total tryptophan kept constant;
unchanged uptake when bolus free tryptophan was kept constant and total tryptophan decreased. Brain tryptophan uptake from a buffer bolus was decreased by large neutral amino acids.
Plasma total tryptophan could be rapidly decreased and free tryptophan increased by briefly disturbing food deprived rats. When free tryptophan concentration rose markedly there was an associated increase of brain tryptophan and 5HT turnover. Studies of shock provoked analgesia in rats and cortical evoked potentials in man both suggest that physiological variations of serotonergic activity are sufficient to influence these measures. This raises the possibility that moderate changes of tryptophan supply to the brain could, in some circumstances, alter serotonergic activity. Brain tryptophan hydroxylase, the rate-limiting enzyme for 5HT synthesis is unsaturated with its substrate under physiological conditions (Eccleston et al., 1965; Friedman et al., 1972). Therefore the supply of tryptophan to the brain influences the amount of 5HT synthesised therein. A large literature reports that variables affecting this supply alter brain tryptophan and 5HT synthesis in the appropriate direction: e.g. plasma tryptophan concentration (Fernstrom and Wurtman, 1971; Gal et al., 1978); its binding to albumin (Knott and Curzon, 1972; Gessa and Tagliamonte, 1974; Bloxam and Curzon, 1978); the degree to which it is freed from albumin as the blood passes through the brain (Pardridge, 1979); plasma concentrations of amino acids competing with tryptophan for transport to the brain (Fernstrom and Wurtman, 1972; Fernstrom et al., 1973); kinetic characteristics of the transport system (James et al., 1978; Mans et al., 1979). Much of this material has been recently reviewed (Curzon, 1979; Fernstrom, 1979).
KeywordsLarge Neutral Amino Acid Tryptophan Concentration Plasma Tryptophan Unesterified Fatty Acid Free Tryptophan
Unable to display preview. Download preview PDF.
- Curzon, G., 1979. Relationships between plasma, CSF and brain tryptophan. J. Neural Trans., Suppl. 15: 81.Google Scholar
- Curzon, G. and Greenwood, M.H., 1974. Plasma protein binding: free and bound tryptophan. Proc. 9th Cong. C.I.N.P., Excerpta Medica Int. Cong. series, 349: 108.Google Scholar
- Curzon, G., Kantamaneni, B.D., Van Boxel, P., Gillman, P.K., Bartlett, J.R. and Bridges, P.K., 1980. Substances related to 5-hydroxytryptamine in plasma and in lumbar and ventricular fluids of psychiatric patients. Acta Psychiat. Scand., in the press.Google Scholar
- Daniel, P.M., Love, E.R., Moorhouse, S.R. and Pratt, O.E., 1980. The effect of insulin on the influx of tryptophan into the brain of the rabbit. J. Physiol., in the press.Google Scholar
- Eccleston, D., 1974. Comparison of the effects of clofibrate and probenecid on tryptophan in the rat. Aromatic Amino Acids in the Brain (CIBA Symposium, 22 ) p. 230.Google Scholar
- Holder, G.E., Bartlett, J.R., Bridges, P.K., Kantamaneni, B.D. and Curzon, G., 1980. Correlations between transmitter metabolite concentrations in human ventricular cerebrospinal fluid and pattern visual evoked potentials. Brain Res., in the press.Google Scholar
- Fernstrom, J.D., 1979. Diet induced changes in plasma amino acid pattern: effects on the brain uptake of large neutral amino acids and on brain serotonin synthesis. J. Neural Trans., Suppl. 15: 55.Google Scholar
- Gessa, G.L., Tagliamonte, A., 1974. Possible role of free serum tryptophan in the control of brain tryptophan concentration and serotonin synthesis. Adv. Biochem. Psychopharmac. 11: 119.Google Scholar
- Lindberg, S., Ahlfors, U.G., Dencker, S.J., Fruensgaard, K., Hansten, S., Jensen, K., Ose, E. and Pihkanen, T.A., 1979. Symptom reduction in depression after treatment with L-tryptophan or imipramine::item analysis of Hamilton rating scale for depression. Acta psychiat. scand., 60: 287.PubMedCrossRefGoogle Scholar
- Tricklebank, M.D., Hutson, P.H. and Curzon, G., 1980. Correlations between rat brain 5-hydroxytryptamine metabolism and the analgesic response to footshock in non-drug treated rats. This volume.Google Scholar
- Young, A., Oldendorf, W.H., Geller, E. and Braun, L., 1977. Effect of albumin binding and amino acid competition on tryptophan uptake into brain. J. Neurochem., 27: 1015.Google Scholar